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    Summary
    EudraCT Number:2014-000293-20
    Sponsor's Protocol Code Number:INCB18424-362
    National Competent Authority:Spain - AEMPS
    Clinical Trial Type:EEA CTA
    Trial Status:Completed
    Date on which this record was first entered in the EudraCT database:2014-07-22
    Trial results View results
    Index
    A. PROTOCOL INFORMATION
    B. SPONSOR INFORMATION
    C. APPLICANT IDENTIFICATION
    D. IMP IDENTIFICATION
    D.8 INFORMATION ON PLACEBO
    E. GENERAL INFORMATION ON THE TRIAL
    F. POPULATION OF TRIAL SUBJECTS
    G. INVESTIGATOR NETWORKS TO BE INVOLVED IN THE TRIAL
    N. REVIEW BY THE COMPETENT AUTHORITY OR ETHICS COMMITTEE IN THE COUNTRY CONCERNED
    P. END OF TRIAL
    Expand All   Collapse All
    A. Protocol Information
    A.1Member State ConcernedSpain - AEMPS
    A.2EudraCT number2014-000293-20
    A.3Full title of the trial
    INCB 18424-362
    A Randomized, Double-Blind, Phase 3 Study of the JAK1/2 Inhibitor, Ruxolitinib or Placebo in Combination With Capecitabine in Subjects With Advanced or Metastatic Adenocarcinoma of the Pancreas Who
    Have Failed or Are Intolerant to First-Line Chemotherapy
    (The JANUS 1 Study)
    INCB 18424-362
    Estudio en fase III, aleatorizado, doble ciego, sobre el inhibidor JAK1/2, ruxolitinib o placebo combinado con capecitabina en sujetos con adenocarcinoma de páncreas avanzado o metastásico que no respondieron o no toleran la quimioterapia en primera línea
    (Estudio JANUS 1)
    A.3.1Title of the trial for lay people, in easily understood, i.e. non-technical, language
    A randomized, double-blind, study of ruxolitinib or placebo in combination with capecitabine as second line treatment for Subjects With Pancreatic cancer (The JANUS 1 Study)
    Estudio aleatorizado, doble ciego, sobre ruxolitinib o placebo combinado con capecitabina como segunda linea de tratamiento para sujetos con cancer pancreatico (Estudio JANUS 1)
    A.3.2Name or abbreviated title of the trial where available
    The JANUS 1 Study
    Estudio JANUS 1
    A.4.1Sponsor's protocol code numberINCB18424-362
    A.7Trial is part of a Paediatric Investigation Plan No
    A.8EMA Decision number of Paediatric Investigation Plan
    B. Sponsor Information
    B.Sponsor: 1
    B.1.1Name of SponsorIncyte Corporation
    B.1.3.4CountryUnited States
    B.3.1 and B.3.2Status of the sponsorCommercial
    B.4 Source(s) of Monetary or Material Support for the clinical trial:
    B.4.1Name of organisation providing supportIncyte Corporation
    B.4.2CountryUnited States
    B.5 Contact point designated by the sponsor for further information on the trial
    B.5.1Name of organisationIncyte Corporation
    B.5.2Functional name of contact pointClinical Trials Information
    B.5.3 Address:
    B.5.3.1Street AddressExperimental Station, Rt 141 & Henry Clay Road
    B.5.3.2Town/ cityWilmington
    B.5.3.3Post codeDE 19880
    B.5.3.4CountryUnited States
    B.5.5Fax number18554462983
    B.5.6E-mailRegAffairs@incyte.com
    D. IMP Identification
    D.IMP: 1
    D.1.2 and D.1.3IMP RoleTest
    D.2 Status of the IMP to be used in the clinical trial
    D.2.1IMP to be used in the trial has a marketing authorisation Yes
    D.2.1.1.1Trade name Jakafi
    D.2.1.1.2Name of the Marketing Authorisation holderIncyte Corporation
    D.2.1.2Country which granted the Marketing AuthorisationUnited States
    D.2.5The IMP has been designated in this indication as an orphan drug in the Community No
    D.2.5.1Orphan drug designation number
    D.3 Description of the IMP
    D.3.1Product nameruxolitinib
    D.3.2Product code INCB018424
    D.3.4Pharmaceutical form Tablet
    D.3.4.1Specific paediatric formulation No
    D.3.7Routes of administration for this IMPOral use
    D.3.8 to D.3.10 IMP Identification Details (Active Substances)
    D.3.8INN - Proposed INNruxolitinib
    D.3.9.1CAS number 941678-49-5
    D.3.9.2Current sponsor codeINCB018424
    D.3.9.3Other descriptive name(R)-3-(4-(7H-pyrrolo[2,3-d]pyrimidin-4-yl)-1H-pyrazol-1-yl)-3-cyclopentylpropanenitrile phosphate
    D.3.9.4EV Substance CodeSUB31642
    D.3.10 Strength
    D.3.10.1Concentration unit mg milligram(s)
    D.3.10.2Concentration typeequal
    D.3.10.3Concentration number5
    D.3.11 The IMP contains an:
    D.3.11.1Active substance of chemical origin Yes
    D.3.11.2Active substance of biological/ biotechnological origin (other than Advanced Therapy IMP (ATIMP) No
    The IMP is a:
    D.3.11.3Advanced Therapy IMP (ATIMP) No
    D.3.11.3.1Somatic cell therapy medicinal product No
    D.3.11.3.2Gene therapy medical product No
    D.3.11.3.3Tissue Engineered Product No
    D.3.11.3.4Combination ATIMP (i.e. one involving a medical device) No
    D.3.11.3.5Committee on Advanced therapies (CAT) has issued a classification for this product No
    D.3.11.4Combination product that includes a device, but does not involve an Advanced Therapy No
    D.3.11.5Radiopharmaceutical medicinal product No
    D.3.11.6Immunological medicinal product (such as vaccine, allergen, immune serum) No
    D.3.11.7Plasma derived medicinal product No
    D.3.11.8Extractive medicinal product No
    D.3.11.9Recombinant medicinal product No
    D.3.11.10Medicinal product containing genetically modified organisms No
    D.3.11.11Herbal medicinal product No
    D.3.11.12Homeopathic medicinal product No
    D.3.11.13Another type of medicinal product No
    D.8 Information on Placebo
    D.8 Placebo: 1
    D.8.1Is a Placebo used in this Trial?Yes
    D.8.3Pharmaceutical form of the placeboTablet
    D.8.4Route of administration of the placeboOral use
    E. General Information on the Trial
    E.1 Medical condition or disease under investigation
    E.1.1Medical condition(s) being investigated
    Male or female, 18 years or older with histologically or cytologically confirmed adenocarcinoma of the pancreas that is inoperable or metastatic.
    Ser varón o mujer y haber cumplido los 18 años con adenocarcinoma de páncreas confirmado mediante histología o citología, inoperable o metastásico.
    E.1.1.1Medical condition in easily understood language
    Advanced pancreatic cancer
    Cancer pancreatico avanzado
    E.1.1.2Therapeutic area Diseases [C] - Cancer [C04]
    MedDRA Classification
    E.1.2 Medical condition or disease under investigation
    E.1.2Version 17.0
    E.1.2Level LLT
    E.1.2Classification code 10033606
    E.1.2Term Pancreatic cancer non-resectable
    E.1.2System Organ Class 100000004864
    E.1.2 Medical condition or disease under investigation
    E.1.2Version 17.0
    E.1.2Level LLT
    E.1.2Classification code 10033605
    E.1.2Term Pancreatic cancer metastatic
    E.1.2System Organ Class 100000004864
    E.1.3Condition being studied is a rare disease Yes
    E.2 Objective of the trial
    E.2.1Main objective of the trial
    To evaluate and compare the OS of subjects with advanced or metastatic adenocarcinoma of the pancreas when treated with ruxolitinib in combination with capecitabine versus capecitabine alone.
    Evaluar y comparar la SG de los sujetos con adenocarcinoma avanzado o metastásico de páncreas al tratarlos con ruxolitinib en combinación con capecitabina frente al tratamiento con capecitabina sola
    E.2.2Secondary objectives of the trial
    To evaluate and compare the efficacy of the 2 treatment groups with respect to PFS.
    To evaluate and compare the efficacy of the 2 treatment groups with respect to overall tumor response and duration of response.
    To evaluate and compare the safety and tolerability of ruxolitinib in combination with capecitabine versus capecitabine alone.
    Evaluar y comparar la eficacia de los 2 grupos de tratamiento con respecto a la SSP.
    Evaluar y comparar la eficacia de los 2 grupos de tratamiento con respecto a la respuesta general del tumor y la duracion de la respuesta.
    Evaluar y comparar la seguridad y la tolerabilidad de ruxolitinib en combinación con capecitabina frente al tratamiento con capecitabina sola
    E.2.3Trial contains a sub-study No
    E.3Principal inclusion criteria
    Male or female, 18 years or older.
    2. Histologically or cytologically confirmed adenocarcinoma of the pancreas.
    3. Advanced adenocarcinoma of the pancreas that is inoperable or metastatic.
    4. Modified Glasgow Prognostic Score (mGPS) of 1 or 2 as defined below:
    a. mGPS of 1: CRP >10 mg/L and albumin ? 35 g/L
    b. mGPS of 2: CRP >10 mg/L and albumin < 35 g/L
    5. Received 1 prior chemotherapy regimen for advanced or metastatic disease (not including neoadjuvant and/or adjuvant therapy)
    a. Use of a fluoropyrimidine-containing regimen (eg, FOLFIRNOX, FOLFOX, CapeOx, etc) in the first-line setting is permitted provided the subject discontinued treatment for reasons other than disease progression and the subject received ? 2 cycles of therapy. Subjects who received single-agent capecitabine as first-line therapy are not eligible.
    b. There is no restriction on the use of fluoropyrimidine-containing regimens in the neo-adjuvant or adjuvant setting.
    c. History of palliative radiotherapy to disease sites is allowed provided there are other sites of disease or subsequent progression of the disease in the radiation field, and ? 4 weeks have elapsed since the completion of radiotherapy and all treatment-related toxicities have resolved or are at a new stable baseline.
    6. Able to tolerate and benefit from therapy as evidenced by:
    a. Absolute neutrophil count ? 1.5 × 109/L with WBC count < 20 × 109/L.
    b. Platelets ? 75 × 109/L.
    c. Hemoglobin ? 9 g/dL (transfusions are permitted to achieve baseline hemoglobin level).
    d. ALT/AST ? 2.5 × upper limit of normal (ULN); or ? 5 × ULN in the presence of liver metastases.
    Total bilirubin ? 1.5 × ULN; if total bilirubin is > 1.5 × ULN then direct bilirubin must be ? 1.5 × ULN.
    f. Alkaline phosphatase < 3 × ULN.
    g. Lactate dehydrogenase (LDH) < 3 × ULN in the absence of hemolysis.
    h. Creatinine clearance ? 50 mL/min measured or calculated by Cockroft-Gault equation or the estimated glomerular filtration rate (GFR) ? 50 mL/min/1.73 m2 using the MDRD formula.
    i. ECOG performance status 0 to 2j. Body mass index (BMI) > 16 kg/m2 k. Absence of significant concurrent, uncontrolled medical condition including, but not limited to, renal, hepatic, hematological, gastrointestinal, endocrine, pulmonary, cardiac, neurological, cerebral or psychiatric disease.
    l. Able to swallow and retain oral medication.
    7. ? 2 weeks elapsed from the completion of previous treatment regimen and subjects must have recovered or be at a new stable baseline from any related toxicities.
    8. Radiographically measurable or evaluable disease (based on local evaluation).
    a. Measurable lesions may be in the field of prior radiation; however, there must be at least a 4-week period between the last radiation treatment and demonstration of interval progression of the lesion compared with the baseline scan documenting disease status for the lesion to be considered measurable.
    9. Females are either postmenopausal for at least 1 year with documented follicle-stimulating hormone (FSH) > 30 IU/L, are surgically sterile for at least 3 months, or must agree to take appropriate precautions to avoid pregnancy (with at least 99% certainty) from screening through follow-up if of childbearing potential. (Note: Permitted methods that are at least 99% effective in preventing pregnancy should be communicated to the subjects and their understanding confirmed). For all females, the pregnancy test result must be negative at screening.
    10. Males must agree to take appropriate precautions to avoid fathering a child (with at least 99% certainty) from screening through follow-up. (Note: Permitted methods that are at least 99% effective in preventing pregnancy should be communicated to the subjects and their understanding confirmed).
    11. Ability to comprehend and willingness to sign an informed consent form (ICF).
    1.Ser varón o mujer y haber cumplido los 18 años.
    2.Adenocarcinoma de páncreas confirmado mediante histología o citología.
    3.Adenocarcinoma avanzado de páncreas inoperable o metastásico.
    4.Puntuación Pronóstica de Glasgow modificada (mGPS) de 1 o 2 según las definiciones siguientes:
    a.mGPS de 1: CRP >10 mg/l y albúmina ?35 g/l
    b.mGPS de 2: CRP >10 mg/l y albúmina <35 g/l
    5.Haber recibido 1 pauta previa de quimioterapia para la enfermedad avanzada o metastásica (sin incluir el tratamiento neoadyuvante o adyuvante)
    a.Se permite el uso de una pauta con fluoropirimidina (p. ej., FOLFIRNOX, FOLFOX, CapeOx, etc.) en primera línea, siempre y cuando el sujeto haya suspendido el tratamiento por causas ajenas a la progresión de la enfermedad y haya recibido ?2 ciclos de tratamiento. Los sujetos que hayan recibido capecitabina en monoterapia como tratamiento de primera línea no serán aptos.
    b.No está restringido el uso de pautas con fluoropirimidina en el entorno neoadyuvante o adyuvante.
    c.Se permiten los antecedentes de radioterapia paliativa en las localizaciones de la enfermedad, siempre y cuando haya otras localizaciones de la enfermedad o esta siga progresando en el campo de irradiación, hayan transcurrido ?4 semanas desde el final de la radioterapia y se hayan resuelto o se encuentren en una nuevo punto inicial estable todos los efectos tóxicos relacionados con el tratamiento.
    6.Capaz de tolerar y de beneficiarse del tratamiento a juzgar por:
    a.Recuento absoluto de neutrófilos ?1,5 × 109/l, con un recuento de leucocitos <20 × 109/l.
    b.Plaquetas ?75 × 109/l.
    c.Hemoglobina ?9 g/dl (se permiten transfusiones para alcanzar el nivel inicial de hemoglobina).
    d.ALT/AST ?2,5 × límite superior de la normalidad (LSN); o ?5× LSN en presencia de metástasis hepáticas.
    e.Bilirrubina total ?1,5 x LSN; si la bilirrubina total es >1,5 × LSN, entonces la bilirrubina directa debe ser ?1,5 x LSN.
    f.Fosfatasa alcalina <3 x LSN.
    g.Lactato deshidrogenasa (LDH) <3 × LSN en ausencia de hemólisis.
    h.Aclaramiento de creatinina ?50 ml/min medido o calculado según la ecuación de Cockroft-Gault o una filtración glomerular estimada (FG) ?50 ml/min/1,73 m2 usando la fórmula MDER.
    i.Estado general ECOG de 0 a 2 (véase el 0)
    j.Índice de masa corporal (IMC) >16 kg/m2 (véase el 0).
    k.Ausencia de enfermedades importantes concurrentes o no controladas, incluidas, entre otras, las enfermedades renales, hepáticas, hematológicas, gastrointestinales, endocrinas, pulmonares, cardíacas, neurológicas, cerebrales o psiquiátricas.
    l.Capaz de tragar y de retener medicamentos por vía oral.
    7.Haber transcurrido ?2 semanas desde la finalización de la pauta de tratamiento anterior y que los sujetos se hayan recuperado o se encuentren en una nuevo punto inicial estable con respecto a cualquier efecto tóxico relacionado.
    8.Tumor medible o evaluable radiográficamente (según una evaluación local).
    a.Las lesiones medibles pueden encontrarse en el campo de radiación anterior; sin embargo, debe haber transcurrido al menos un periodo de 4 semanas desde el último tratamiento de radioterapia y existir manifestaciones de progresión de la lesión en el intervalo en comparación con la exploración inicial que documente el estado de la enfermedad para que la lesión se considere medible.
    9.Mujeres posmenopáusicas durante al menos 1 año con hormona foliculoestimulante (FSH) documentada >30 UI/l, esterilizadas quirúrgicamente durante al menos 3 meses o que accedan a tomar las precauciones necesarias para evitar embarazos (con al menos una certidumbre del 99 %) desde la selección hasta el seguimiento si están en edad fértil. (Nota: deben explicarse a los sujetos los métodos permitidos que son eficaces al menos en un 99 % para prevenir embarazos y confirmar que lo han comprendido [0]). En todas las mujeres, el resultado de la prueba de embarazo debe ser negativo en la selección.
    10.Los varones deben acceder a tomar las precauciones necesarias para evitar engendrar hijos (con al menos una certidumbre del 99 %) desde la selección hasta el seguimiento. (Nota: deben explicarse a los sujetos los métodos permitidos que son eficaces al menos en un 99 % para prevenir embarazos y confirmar que lo han comprendido [0]).
    11.Capacidad para comprender y voluntad de firmar un formulario de consentimiento informado (FCI).
    E.4Principal exclusion criteria
    1. Received more than 1 prior chemotherapy regimen for advanced or metastatic disease.
    2. Chronic or current active infectious disease requiring systemic antibiotics, antifungal, or antiviral treatment.
    3. Known brain or central nervous system metastases or history of uncontrolled seizures.
    Clinically significant cardiac disease including unstable angina, acute myocardial infarction within 6 months from Day 1 of study drug administration, New York Heart Association Class III or IV congestive heart failure, and arrhythmia requiring therapy.
    5. Ongoing radiation therapy, radiation therapy administered within 30 days of enrollment, or prior history of radiation therapy to ? 25% of the bone marrow.
    Subjects who received palliative radiation treatment to a limited field or on an accelerated schedule within the last 30 days are eligible for enrollment, provided at least 7 days have elapsed from completion of radiation therapy prior to the first dose and all treatment related toxicities have resolved or are at a new stable baseline.
    6. Concurrent anticancer therapy (eg, chemotherapy, radiation therapy, surgery, immunotherapy, biologic therapy, hormonal therapy, investigational therapy, or tumor embolization).
    7. Subjects who participated in any other study in which receipt of an investigational study drug occurred within 28 days or 5 half-lives (whichever is longer) prior to first dose.
    8. Current or previous other malignancy within 2 years of study entry, except cured basal or squamous cell skin cancer, superficial bladder cancer, prostate intraepithelial neoplasm, carcinoma in situ of the cervix, or other noninvasive or indolent malignancy without sponsor approval.
    9. Recent (? 3 months) history or ongoing partial or complete bowel obstruction, unless due to the disease understudy and surgically corrected.
    10. PPrior severe reaction to fluoropyrimidines, known DPD deficiency, or other known hypersensitivity to active substances including fluorouracil (5-FU), ruxolitinib, or any of their excipients
    11. Known history of human immunodeficiency virus (HIV) infection.
    12. Active hepatitis B or C infection that requires treatment.
    13. Unwilling to be transfused with blood components.
    14. Pregnant or breastfeeding women.
    15. Subjects who, in the opinion of the investigator, are unable or unlikely to comply with the dosing schedule and study evaluations.
    16. Any condition in the judgment of the investigator that would jeopardize the safety of the subject or compliance with the protocol.
    1.Haber recibido más de 1 pauta previa de quimioterapia para enfermedad avanzada o metastásica.
    2.Enfermedad infecciosa activa crónica o actual que requiera la administración de antibióticos, antifúngicos o antivíricos sistémicos.
    3.Metástasis conocidas cerebrales o en el sistema nervioso central, o antecedentes de convulsiones incontroladas.
    4.Cardiopatía clínicamente significativa, lo que incluye angina inestable, infarto agudo de miocardio en los 6 meses siguientes al día 1 de la administración del fármaco del estudio, insuficiencia cardíaca congestiva de clase III o IV según la Asociación Cardíaca de Nueva York (New York Heart Association, NYHA) y arritmia que requiera tratamiento.
    5.Tratamiento de radioterapia en curso o administrado en los 30 días siguientes a la inscripción, o antecedentes de radioterapia en ?25 % de la médula ósea
    a.Los sujetos que hayan recibido radioterapia paliativa en un campo limitado o según un programa acelerado en los 30 últimos días serán aptos para su inscripción, siempre y cuando hayan transcurrido al menos 7 días desde la finalización de la radioterapia antes de la primera dosis y se hayan resuelto o hayan alcanzado una nuevo punto inicial estable todas las toxicidades relacionadas con el tratamiento.
    6.Tratamiento oncológico concomitante (p. ej., quimioterapia, radioterapia, cirugía, inmunoterapia, tratamiento biológico, tratamiento hormonal, tratamientos en investigación o embolización tumoral).
    7.Sujetos que hayan participado en cualquier otro estudio en el que se haya administrado otro fármaco de un estudio en investigación en los 28 días o 5 semividas (el periodo más largo) previos a la primera dosis.
    8.Otra neoplasia actual o previa en los 2 años anteriores al ingreso en el estudio, excepto carcinoma basocelular o espinocelular curado, cáncer de vejiga superficial, neoplasia intraepitelial prostática, carcinoma cervical localizado u otras neoplasias malignas no invasivas o indolentes sin autorización previa del promotor.
    9.Antecedentes recientes (?3 meses) de obstrucción intestinal parcial o total, salvo que se haya debido a la enfermedad estudiada y se haya corregido quirúrgicamente.
    10.Reacción anterior intensa a las fluoropirimidinas, deficiencia conocida de dihidropirimidina-deshidrogenasa (DPD) u otra hipersensibilidad conocida a las sustancias activas incluyendo el fluorouracilo (5-FU), ruxolitinib, o a cualquiera de sus excipientes.
    11.Antecedentes conocidos de infección por el virus de la inmunodeficiencia humana (VIH).
    12.Infección activa por el virus de la hepatitis B o C que requiera tratamiento.
    13.Rechazo a que se le transfundan hemoderivados.
    14.Mujeres embarazadas o en período de lactancia.
    15.Sujetos que, en opinión del investigador, no puedan o no es probable que puedan cumplir la pauta posológica y realizar las evaluaciones del estudio.
    16.Cualquier afección que, en opinión del investigador, pueda poner en peligro la seguridad del sujeto o el cumplimiento del protocolo.
    E.5 End points
    E.5.1Primary end point(s)
    Overall survival as determined from the date of randomization until death due to any cause.
    La supervivencia general calculada desde la fecha de la aleatorización hasta la de muerte por cualquier causa.
    E.5.1.1Timepoint(s) of evaluation of this end point
    This study is event-driven and will complete when 262 deaths (combined across the 2 treatment groups) occur in the study, presuming that the study will not have been stopped earlier for futility, efficacy, or safety considerations.
    In this study, approximately 310 subjects will be randomized 1:1 between ruxolitinib and placebo over an approximate 18-month period. Assuming uniform accrual over the 18-month period, exponential survival on both placebo (median OS of 2 months) and ruxolitinib (median OS of 3 months), the targeted number of deaths is expected 2 months after the last subject starts treatment in the randomized portion of the study.
    Este estudio estara motivado por los acontecimientos y finalizara cuando se produzcan 262 muertes (entre los 2 grupos de tratamiento combinados) en el estudio, suponiendo que este no haya finalizado antes por cuestiones de futilidad, eficacia o seguridad.
    En este estudio se aleatorizara aproximadamente a 310 sujetos 1:1 entre ruxolitinib y placebo durante un periodo aproximado de 18 meses. Suponiendo una acumulación uniforme a lo largo de los 18 meses, la supervivencia exponencial con placebo (mediana de SG de 2 meses) y con ruxolitinib (mediana de SG de 3 meses), se espera alcanzar el numero de muertes previsto 2 meses despues de que el último sujeto comience el tratamiento en la parte aleatorizada del estudio.
    E.5.2Secondary end point(s)
    Progression-free survival defined as the time from randomization until the earliest date of disease progression determined by investigator assessment of objective radiographic disease assessments per RECIST (v1.1), or death due to any cause, if sooner.

    Objective response rate and duration of response determined by radiographic disease assessments per RECIST (v1.1), by investigator assessment.

    Safety and tolerability of the treatment regimens through assessment of AEs and changes in safety assessments including laboratory parameters.
    Supervivencia sin progresion definida como el tiempo transcurrido desde la aleatorización hasta la primera fecha de progresion de la enfermedad calculada por el investigador mediante una evaluacion radiografica objetiva segun los Criterios de Evaluación de la Respuesta en Tumores Sólidos (Response Evaluation Criteria in Solid Tumors, RECIST) (version 1.1) o hasta la muerte por cualquier causa, si se produce antes.

    Tasa de respuesta objetiva y duracion de la respuesta segun las evaluaciones radiograficas efectuadas por el investigador segun los criterios RECIST (version 1.1).

    Seguridad y tolerabilidad de las pautas de tratamiento mediante la evaluacion de los acontecimientos adversos y de los cambios producidos en las evaluaciones de la seguridad, incluidos los parámetros analiticos.
    E.5.2.1Timepoint(s) of evaluation of this end point
    This study is event-driven and will complete when 262 deaths (combined across the 2 treatment groups) occur in the study, presuming that the study will not have been stopped earlier for futility, efficacy, or safety considerations.
    In this study, approximately 310 subjects will be randomized 1:1 between ruxolitinib and placebo over an approximate 18-month period. Assuming uniform accrual over the 18-month period, exponential survival on both placebo (median OS of 2 months) and ruxolitinib (median OS of 3 months), the targeted number of deaths is expected 2 months after the last subject starts treatment in the randomized portion of the study.
    Este estudio estara motivado por los acontecimientos y finalizara cuando se produzcan 262 muertes (entre los 2 grupos de tratamiento combinados) en el estudio, suponiendo que este no haya finalizado antes por cuestiones de futilidad, eficacia o seguridad.
    En este estudio se aleatorizara aproximadamente a 310 sujetos 1:1 entre ruxolitinib y placebo durante un periodo aproximado de 18 meses. Suponiendo una acumulación uniforme a lo largo de los 18 meses, la supervivencia exponencial con placebo (mediana de SG de 2 meses) y con ruxolitinib (mediana de SG de 3 meses), se espera alcanzar el numero de muertes previsto 2 meses despues de que el último sujeto comience el tratamiento en la parte aleatorizada del estudio.
    E.6 and E.7 Scope of the trial
    E.6Scope of the trial
    E.6.1Diagnosis No
    E.6.2Prophylaxis No
    E.6.3Therapy Yes
    E.6.4Safety Yes
    E.6.5Efficacy Yes
    E.6.6Pharmacokinetic Yes
    E.6.7Pharmacodynamic Yes
    E.6.8Bioequivalence No
    E.6.9Dose response No
    E.6.10Pharmacogenetic No
    E.6.11Pharmacogenomic No
    E.6.12Pharmacoeconomic No
    E.6.13Others No
    E.7Trial type and phase
    E.7.1Human pharmacology (Phase I) No
    E.7.1.1First administration to humans No
    E.7.1.2Bioequivalence study No
    E.7.1.3Other No
    E.7.1.3.1Other trial type description
    E.7.2Therapeutic exploratory (Phase II) No
    E.7.3Therapeutic confirmatory (Phase III) Yes
    E.7.4Therapeutic use (Phase IV) No
    E.8 Design of the trial
    E.8.1Controlled Yes
    E.8.1.1Randomised Yes
    E.8.1.2Open No
    E.8.1.3Single blind No
    E.8.1.4Double blind Yes
    E.8.1.5Parallel group Yes
    E.8.1.6Cross over No
    E.8.1.7Other No
    E.8.2 Comparator of controlled trial
    E.8.2.1Other medicinal product(s) No
    E.8.2.2Placebo Yes
    E.8.2.3Other No
    E.8.2.4Number of treatment arms in the trial2
    E.8.3 The trial involves single site in the Member State concerned No
    E.8.4 The trial involves multiple sites in the Member State concerned Yes
    E.8.4.1Number of sites anticipated in Member State concerned17
    E.8.5The trial involves multiple Member States Yes
    E.8.5.1Number of sites anticipated in the EEA60
    E.8.6 Trial involving sites outside the EEA
    E.8.6.1Trial being conducted both within and outside the EEA Yes
    E.8.6.2Trial being conducted completely outside of the EEA No
    E.8.6.3If E.8.6.1 or E.8.6.2 are Yes, specify the regions in which trial sites are planned
    Australia
    Canada
    European Union
    Korea, Republic of
    New Zealand
    Taiwan
    Thailand
    United States
    E.8.7Trial has a data monitoring committee Yes
    E.8.8 Definition of the end of the trial and justification where it is not the last visit of the last subject undergoing the trial
    This study is event-driven and will complete when 262 deaths (combined across the 2 treatment groups) occur in the study, presuming that the study will not have been stopped earlier for futility, efficacy, or safety considerations.
    Este estudio estara motivado por los acontecimientos y finalizara cuando se produzcan 262 muertes (entre los 2 grupos de tratamiento combinados) en el estudio, suponiendo que este no haya finalizado antes por cuestiones de futilidad, eficacia o seguridad.
    E.8.9 Initial estimate of the duration of the trial
    E.8.9.1In the Member State concerned years2
    E.8.9.1In the Member State concerned months0
    E.8.9.1In the Member State concerned days0
    E.8.9.2In all countries concerned by the trial years2
    E.8.9.2In all countries concerned by the trial months0
    E.8.9.2In all countries concerned by the trial days0
    F. Population of Trial Subjects
    F.1 Age Range
    F.1.1Trial has subjects under 18 No
    F.1.1.1In Utero No
    F.1.1.2Preterm newborn infants (up to gestational age < 37 weeks) No
    F.1.1.3Newborns (0-27 days) No
    F.1.1.4Infants and toddlers (28 days-23 months) No
    F.1.1.5Children (2-11years) No
    F.1.1.6Adolescents (12-17 years) No
    F.1.2Adults (18-64 years) Yes
    F.1.2.1Number of subjects for this age range: 140
    F.1.3Elderly (>=65 years) Yes
    F.1.3.1Number of subjects for this age range: 170
    F.2 Gender
    F.2.1Female Yes
    F.2.2Male Yes
    F.3 Group of trial subjects
    F.3.1Healthy volunteers No
    F.3.2Patients Yes
    F.3.3Specific vulnerable populations Yes
    F.3.3.1Women of childbearing potential not using contraception No
    F.3.3.2Women of child-bearing potential using contraception Yes
    F.3.3.3Pregnant women No
    F.3.3.4Nursing women No
    F.3.3.5Emergency situation No
    F.3.3.6Subjects incapable of giving consent personally No
    F.3.3.7Others No
    F.4 Planned number of subjects to be included
    F.4.1In the member state21
    F.4.2 For a multinational trial
    F.4.2.1In the EEA 100
    F.4.2.2In the whole clinical trial 310
    F.5 Plans for treatment or care after the subject has ended the participation in the trial (if it is different from the expected normal treatment of that condition)
    None
    Ninguno
    G. Investigator Networks to be involved in the Trial
    N. Review by the Competent Authority or Ethics Committee in the country concerned
    N.Competent Authority Decision Authorised
    N.Date of Competent Authority Decision2014-08-13
    N.Ethics Committee Opinion of the trial applicationFavourable
    N.Ethics Committee Opinion: Reason(s) for unfavourable opinion
    N.Date of Ethics Committee Opinion2014-07-11
    P. End of Trial
    P.End of Trial StatusCompleted
    P.Date of the global end of the trial2016-12-22
    As of 1.2.2020, the UK is no longer an EU Member State. However, EU law still applies to the UK during the transition period
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